studies on the optimum management of paracetamol poisoning

Abstract

paracetamol is the most common medicinal substance involved in self poisoning in the UK.Nacetylcysteine (NAC)is used orally or intravenously for treatment of paracetamol overdose .The most serious adverse effect of intravenous NAC is anaphylactoid reaction.In this work I have examined 1)the role of the aminoacid,taurine as a biomarker in paracetamol poisoning 2) markers of reactions to NAC, 3) methods to reuce the incidence of adverse events related to NAC use and 4) the pharmacokinetics and effects of taurine administered exogenously to normal volunteers. IN this work,I have shown that approximately 37 of admissions to the poisons Unit at L1andough Hospital in cardiff over a 14year period (19892002)involved paracetamol,making it the commonest medicinal substance in overdose and the commonest substance involved after alchol .I have observed significant increases in plasma taurine concentration after paracetamol poisoning.However ,this biomarker does not appear to be sufficiently specific for clinical purpose.I have demonstrated that infusion of NAC in healthy volunteers increases plasma histamine concentrations by 90 within 15 min.I have also described the plasma concentrations and effects of intravenous NAC in healthy volunteers ,and demonstrated that administration of the cyclooxygenase inhibitor,naproxen,may ameliorate to some extent some of the adverse effects of intravenous NAC in these individuals.Finally ,I have shown that taurine is absorbed relatively rapidly after oral administration of a tablet formulation ,and declines in plasma with a half life of elimination of approximately 1.5+_ 0.6 (SD) hours in healthy volunteers .This information is novel ,and may be of value in examining a putative role of turine in paracetamol poisoning in man in the future.